P1370: EFFECTS OF CLONAL HEMATOPOIESIS OF INDETERMINATE POTENTIAL FROM HEALTHY DONORS ON RECIPIENTS AFTER TRANSPLANTATION AND RELATED RESEARCH
Authors: B. Shen, E. Jiang
Journal: HemaSphere (2022)

Background: Allogeneic hematopoietic stem cell transplantation is an important method for treating hematologic malignant. However, Finding an HLA-matched donor has always been a significant obstacle and limited the therapy. Still, with the development of haploid-HSCT, this problem has been effectively solved. However, some donors had been found carrying malignant hematopathy-related mutation genes when they had a physical examination. But these donors do not have any clinical manifestations of hematopathy or related history. To distinguish it from clonal hematopoiesis, We called this Clonal hematopoiesis of indeterminate potential（CHIP）. There is little research on the effects of transplanting cells carrying mutated genes on patients, so we explored this. Aims: To analyze the situation of Clonal hematopoiesis of indeterminate potential（CHIP） in healthy donors, to investigate the effects of CHIP-carrying hematopoietic cells on the survival and relapse of recipients after transplantation, and to screen out the types of gene mutations associated with poor prognosis of recipients. Methods: Healthy donors who were examined at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from August 2015 to August 2020 were screened for the hematological tumor gene mutations, The effects of CHIP+ and CHIP- hematopoietic cells on graft engraftment, patient survival, disease recurrence and acute graft-versus-host disease (aGVHD) were compared. SPSS22.0 and GraphPad Prism 8 were used to analyze the data. Results: A total of 351 donors underwent hematological tumor genetic testing, including 223 males (63.53%) and 128 females (36.47%). 147 (41.88%) were positive for gene mutation and 204 (58.12%) were negative for gene mutation. Among the patients with positive gene mutation, there were 93 males with a composition ratio of 41.70% and 54 females with a composition ratio of 42.18%. The top five mutant genes carried by donors were FAT1, NOTCH1, RELN, SETBP1 and KMT2D; The proportion of CHIP among donors in different age groups was similar, about 25%. There were no statistical differences in post-transplant survival, cumulative relapse rate, graft engraftment time, and incidence of aGVHD between chip group and non-CHIP group (p>0.05); Survival analysis was performed on the gene mutations carried by the donors, JAK2 and CREBBP were associated with poor prognosis of patients, (p= 0.001 and p= 0.01, respectively); The variables with univariate analysis P<0.1 were included in multivariate analysis, and the results showed that JAK2 was an independent risk factor for poor survival prognosis, p=0.03. Summary/Conclusion: About 42% of the healthy donors carry CHIP; CHIP exists in all age groups, and the incidence is similar; Donor CHIP has no significant effect on graft engraftment, disease relapse, and aGVHD occurrence; JAK2 gene mutation carried by donors is associated with a poor survival prognosis of patients.